Reference also is made to U.S. Pat. Nos. 3,539,455 and 4,340,448, the entire disclosures of which hereby are incorporated by reference. Such patents disclose, for example, approaches to measuring certain materials in the presence of specified enzymes of such materials, for example glucose in the presence of glucose oxidase, etc.
U.S. Pat. No. 3,539,455 discloses a technique for measuring the concentration of glucose by allowing the glucose to diffuse through a membrane into an electrolyte that contains an enzyme, particularly an oxidase, such as glucose oxidase. In the electrolyte a reaction occurs to produce hydrogen peroxide. The electrical current produced during that reaction is measured as a representation of, for example, the glucose concentration. When there is interfering material in the unknown sample, which also contains the glucose, for example, means are provided by the patentee to subtract the current produced by the intefering material from the current produced by the interfering material and that material whose concentration is to be measured. The device of the U.S. Pat. No. 3,539,455 suffers from inaccuracy and instability due to the relatively low signal strength and, as the patentee recognizes, the difficulty in maintaining a uniform oxidase layer at the membrane.
In U.S. Pat. No. 4,340,448 the need for an electrolyte separate from the unknown material, separated therefrom by a selective diffusing membrane, is overcome by immobilizing the enzyme directly on the cathode (working electrode) of the sensor system. The cathode and reference electrode both are inserted into an electrolyte that contains the unknown concentration of material intended for measurement. Such immobilization is achieved by confining the enzyme in a gel that is applied to the working electrode; the gel permits oxygen and glucose to diffuse therethrough.
In the above mentioned application Ser. No. 407,566, there is disclosed an apparatus and method for making electrochemical measurements of certain species, especially of the type that undergo oxidation and/or reduction reactions. The invention disclosed in such application employs a cathode (working electrode), reference electrode, and counter electrode, and these are connected to function in a potentiostat mode. Accordingly, the reactions occurring at the cathode and counter electrode are equal and opposite so that there is no consumption of the electrochemically active species (oxygen, for example), and highly accurate current measurements as a function of the concentration of such species can be made. A particular advantage to such sensor system is the ability to miniaturize the same, including the possibility of placing the three electrodes on a single support that may be placed and used intravivo, while providing improved accuracy and stability by the preferred forms of electrodes and the relatively large signals produced thereby.
As used herein "fluids" includes gases, liquids, vapors, mixtures thereof, and virtually any other material in which an electrochemically active species may occur and/or be detected. In the preferred embodiment and best mode of the invention described below, the electrochemically active species is described as oxygen; however, the electrochemically active species may be other than oxygen. Moreover, although the preferred embodiment and best mode of the invention will be described below with reference to detection of glucose in the presence of glucose oxidase enzyme, it will be appreciated that the principles of the invention may be employed to detect materials other than glucose in the presence of other enzymes.